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| Lanthanum Carbonate, a Phosphate Binder, Inhibits Calcification of Implanted Aortic Allografts |
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Osamu Kinoshita1, Noboru Motomura1, Haruo Yamauchi2, Minoru Ono1, Arata Murakami1, Shinichi Takamoto2; 1Cardiothoracic Surgery, The University of Tokyo, Tokyo, Japan; 2Mitsui Memorial Hospital, Tokyo, Japan Objective: Calcification is the most major postoperative problem of implanted aortic allografts (AAs) and tends to appear more frequent and earlier in young recipients. It is reported that this early calcification of AAs in young recipients is partly due to physiological hyperphosphatemia of young recipients. Hyperphosphatemia and ectopic calcification are critical issues for uremic patients, and phosphate binders are used clinically. We hypothesized that phosphate binders, lanthanum carbonate (LC) and calcium carbonate (CC), inhibit calcification of implanted AAs in young recipients, and verified this hypothesis using rat experimental model. Methods: Aorta was harvested from a 4 week-old BN rat and implanted into subcutaneous space of a 4 week-old LEW rat. Recipient LEW rats were divided into 3 groups, group-N (g-N), group-L (g-L), and group-C (g-C). G-N was fed by normal diets (MF; Oriental Yeast Co., Ltd., Japan), g-L by MF plus 3% by weight of LC, g-C by MF plus 3% by weight of CC. All groups were composed of 9 rats. The implanted AAs were explanted 2 weeks after implantation. Calcification of AAs was evaluated qualitatively by Von Kossa stain and quantitatively by calcium (Ca) content assay using atomic absorption analysis method. Calcification score in Von-Kossa stain was defined as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Ca content was standardized dividing by dry graft weight. Blood samples were taken by right atrial puncture and centrifuged immediately to obtain serum. Serum Ca and phosphorus (Pi) concentration were measured. Data are expressed as mean ± SEM and comparisons between groups were made using t-test. A value of P < 0.05 was considered significant. Results: Calcification score of g-N, g-L, and g-C were 2.6 ± 0.2, 1.2 ± 0.4, and 0.8 ± 0.4, respectively. Ca content per 1 g dry graft of g-N, g-L, and g-C were 48.9 ± 8.7, 15.8 ± 3.4, and 8.9 ± 3.4 mg, respectively. Calcification was significantly inhibited by LC and CC. Serum Ca of g-N, g-L, and g-C were 11.5 ± 0.3, 12.2 ± 0.2, and 13.5 ± 0.4 mg/dL, respectively. Serum Ca of g-C was significantly high than that of g-N and g-L. Serum Pi of g-N, g-L, and g-C were 15.4 ± 0.3, 12.5 ± 0.5, and 11.7 ± 0.4 mg/dL, respectively. Both LC and CC reduced serum Pi significantly. Conclusion: Phosphate binders, LC and CC, inhibit calcification of implanted AAs in young rat subdermal implantation model. CC induced significant hypercalcemia and LC has a more potential for clinical use. Back to 2010 Annual Meeting Back to Program Outline Back to Main Program |
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